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Title page for ETD etd-04152014-143121

Type of Document

Dissertation

Author

Campbell, Nicholas George

URN

etd-04152014-143121

Title

Rare variants affecting regulation of serotonin and dopamine transport contribute to the genetic liability of autism

Degree

PhD

Department

Neuroscience

Advisory Committee

Advisor Name

Title

Karoly Mirnics

Committee Chair

James Sutcliffe

Committee Member

Randy Blakely

Committee Member

Thomas Morgan

Committee Member

Keywords

serotonin

dopamine

genetics

neuroscience

autism

Date of Defense

2013-12-16

Availability

unrestricted

Abstract

Autism spectrum disorder (ASD) is a neuropsychiatric condition with a range of deficits in social reciprocity and communication, and patterns of rigid-compulsive behaviors. ASD prevalence is estimated at approximately 1 in 100 individuals, with substantial evidence for a largely genetic etiology of complex architecture. The work described here is based on the principle that genes involved in the etiology of ASD will converge onto shared biological systems, and those systems will inform investigation into the pathogenesis of ASD. The purpose of this work was to test the hypothesis that genes encoding monoamine regulation networks harbor genetic variants associated with ASD. In part this was driven by the phenomenon of “hyperserotonemia” in a third of ASD cases. Genes in monoamine networks were thus analyzed for presence of ASD associated variation, and downstream functional studies of two such proteins, the adenosine A3 receptor (a regulator of the serotonin transporter) as well as the dopamine transporter, were revealed novel abnormalities. In conclusion, the results are highly supportive that both a genetic and functional liability exists within the broad context of monoamine dysfunction and ASD.